TEMPO-2 Trial Shows Promise for Tavapadon in Newly Diagnosed Parkinson’s Disease

For years, the dopaminergic medication levodopa has been the gold standard therapy for motor symptom relief in patients newly diagnosed with Parkinson’s disease.

“Levodopa is the most efficacious oral medication we have thus far, and approximately 90% of patients with early-stage Parkinson’s disease are prescribed the drug,” says Hubert Fernandez, MD, Director for the Center of Neurological Restoration at Cleveland Clinic and an expert in movement disorders. “However, it can cause motor fluctuations and dyskinesias in some patients.”

Dr. Fernandez is global principal investigator on a series of four multi-center, randomized clinical trials evaluating the safety, efficacy and tolerability of tavapadon, a novel dopamine agonist for Parkinson’s symptom management that selectively targets D1 and D5 receptors.

AbbVie, which developed the drug and will market it as Juvmo, recently announced that tavapadon has received approval from the U.S. Food and Drug Administration.

Four TEMPO studies paved the way:

• TEMPO-1and TEMPO-2 trialed tavapadon as a monotherapy in newly diagnosed patients. TEMPO-1 was a three-arm, fixed-dose study, with participants randomly assigned to a low dose, high dose or placebo. TEMPO-2 participants were randomly assigned to flexible-dose tavapadon or placebo.
• TEMPO-3 trialed tavapadon as an adjunctive therapy to levodopa in patients with moderate to advanced Parkinson’s disease.
• TEMPO-4 is an ongoing open-label extension trial evaluating patients for 58 weeks to assess long-term safety and efficacy.

Results of the TEMPO-1 and TEMPO-3 trials were published online in JAMA Neurology in March 2026. More recently, full results from the Phase 3 TEMPO-2 trial were published in The Lancet Neurology in August 2026.

“The results from TEMPO-2 are groundbreaking because the improvements in Parkinson’s disease motor symptoms and activities of daily living scores were significant,” says Dr. Fernandez. “It’s been decades since an FDA application has been received for early monotherapy other than levodopa based on a positive pivotal trial.”

Clinically meaningful results

TEMPO-2 was conducted at 75 clinical sites across 13 countries. Between January 2020 and February 2024, 304 participants with early-stage Parkinson’s (less than three years’ disease duration) who were treatment-naïve or had less than three months of previous dopaminergic treatment were randomly assigned 1:1 to flexible-dose tavapadon (5 to 15 mg) or placebo. Tavapadon was titrated over six weeks to a 5 mg once-daily dose with a dose adjustment up to 15 mg by week 14 as tolerated.

The efficacy of flexible-dose tavapadon was evaluated using a combined score from the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II (subjective scale answered by patients on motor aspects of activities of daily living) and Part III (objective motor evaluation conducted by investigators). The primary endpoint was change from baseline to week 26.

There was a 9.1-point improvement in the MDS-UPDRS Parts II and III combined score for participants on tavapadon relative to placebo at week 26.

“That represents a significant and clinically meaningful improvement in Parkinson’s disease motor symptoms, such as tremor, stiffness, slowness and balance,” says Dr. Fernandez. “In addition, there were very low incidences of somnolence and impulse control disorders — idiosyncratic side effects that are common among first-generation dopamine agonists targeting the D2 family of receptors that have been on the market for three decades.”

While the results are encouraging, the ongoing TEMPO-4 trial is pivotal to evaluating whether idiosyncratic side effects show up six to 12 months after participants begin low-dose, high-dose or flexible-dose tavapadon.

“TEMPO-1, -2 and -3 have shown that tavapadon improves day-to-day function in Parkinson’s patients, and it improves their physical score,” says Dr. Fernandez. “TEMPO-4 will provide a lot of information on the long-term safety and tolerability of the medication.”

Next steps for research

Dr. Fernandez is also curious about the ideal titration for tavapadon that might allow patients to better tolerate the medication. During TEMPO-2, participants adhered to a set titration schedule. Those who were unable to reach the minimum 5 mg dose or couldn’t tolerate the rigid titration schedule were discontinued from the trial. (Fifty-seven patients assigned to flexible-dose tavapadon prematurely discontinued the study, with 36 attributed to adverse events. Most adverse events were not serious and were mild to moderate in severity.)

Looking ahead, Dr. Fernandez would like to study the efficacy and tolerability of tavapadon on a broader group of patients with Parkinson’s disease.

“We’ve tested it on newly diagnosed patients and in those with moderate to advanced Parkinson’s. But there is a whole group in between,” he says. “How early or late can tavapadon be given? This may require some real-world experience and individualized titration.”

For now, Dr. Fernandez says the TEMPO-1 and TEMPO-2 clinical trials have shown that once-daily tavapadon “is going to be a big boost for newly diagnosed, younger Parkinson’s patients with a long runway ahead of them. Those with milder motor severity may be able to hold off on levodopa at first, avoid unwanted side effects and then begin taking it later in life as an adjunctive therapy with tavapadon.”